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duction: Well-difrecurrence rate isentiated liposarco which are potessed in DDLS. A

grafts (3). A non-an early marker

colysis has the pin a human DD

mycin), an anthr

Pα has been shows and cell deathomerase II com

ased effectivenesSep 1;70(17):6891-ncol (Meeting AbstReson Med 2004;5

MRS assessmenAsif Rizwan1, Xiaorial Sloan-Ketter

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fferentiated/dedifs high even if maoma (DDLS) leavntial therapeutic

Administration of -invasive markerr of response/nopotential to be a DLS tumor xenoracycline used to

wn to induce celh. Adria is an anmplex. While furthss compared to a901. Epub 2010 Auracts) 2010;28(15_

52(4):902-906. 6. Ti

nt of lactate inaohui Ni1, Rachaelring Cancer Centetes, 3Radiology, M

fferentiated liposargins are negatves non-surgical targets (1,2). Fothe SN-38 prodr

r reflecting the en-response coulbiomarker of pr

ograft (DDLS BWo treat sarcomas.

ll growth arrest (ntimitotic and cyther investigationagents which inteug 16. 2. Gobble R_suppl):10005. 4. imchenko, NA, Wild

n dedifferential O'Connor2, Samu

er, New York, NY, Memorial Sloan-Ket

sarcomas occur tive and de-differcandidates with

or example, CEBrug CPT11 (irino

effect of such agd permit the phyrognosis and treaWH) implanted i

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sacrifi4583, were ofixed iby heby thevolumCPT1treatevs conhad salthouCPT1showe(PIMOgrowthvascuweek develo

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6). CPT-11 is alstotoxic agent whn is needed, ourerfere with DNA RM, Qin LX, et. al..He, Q.,Shungu, D.de, M., et. al. Gene

ated liposarcomuel Singer2, Sean CUnited States, 2Surttering Cancer Ce

mainly in the abrentiation is predfew options. Re

BPα, which is a otecan) caused inents could be qu

ysician to disconatment effect. Thn mice in respo

Methomice atumor Adria-MRI/Min 7 cwere i.p.) wscan. the Mhome were thicknTE = detectCoherobtainexcitaPeak lactateHistol

ydrochloride (PIM0 and 40 mg/dministered via

ce (Hoechst 333Sakura Finetek

obtained using ain 4% paraformamatoxylin/eosin

e slice volume anme and concentra

1-treated (Fig-1Ad group had lowntrol, P = 0.0006significantly loweugh lactate had d1 vs. control, P <ed regions of redO) in the growingh-halted CPT-11larized and free in the Adria andopment of necroscussion. As earompanied by groors. The mechaer investigation

erentiation resultso known to inhi

hich interferes wr data suggest trepair/replicationCancer Res. 2011 C., et. al. J. Magn

es Dev. 1996 Apr 1

ma models treCarlin3, Jason Kourgery, Memorial S

enter, New York, N

bdomen, and surdictive of poor ouecent investigatio

transcription facncreased CEBPαuite valuable in tinue ineffective he goal of the conse to CPT-11

ods. Overview:and monitored ur growth delay stu-treated, and 5 MRSI was perforcontrol, 6 Adria-treated twice pe

with the first treaMR Experimen

MR experiments built 2-turn soleused. T2-weigh

ness = 1 mm, nu40 ms, matrix= tion was perforence (Sel-MQCned from a 5-mmations =512, 102

fitting was perfe was performelogy: SelectedMO) (hypoxypro/kg, respectivelythe tail vein at 1

342). Tumors wek), snap-frozen aa cryostat microtoaldehyde then blstaining. Data A

nd compared to tation. Results: TA). Adria had litt

wer lactate than th6 for CPT11 vs er lactate concdecreased in the< 0.0001 for CPTduced cell densitg control and Ad1-treated tumors

of hypoxia. The control groups isis as seen on hrly as 3 days afteowth arrest in Canism by which n. One could ts in a conversbit the activity of

with DNA repair bthat the CPT-11n. References ( Apr 1;71(7):2697-

n. Reson B. 106(3);10(7):804-15

eated with cheutcher1, and KristenSloan-Kettering CaNY, United States

rgery is the maiutcome. The lackons have revealector involved in aα expression andpre-clinical drugtreatment withourrent study was. A second coh

35 BWH tumorsuntil the volume udies, tumor voluCPT-11-treated

rmed serially at d-treated, and 5 er week (Adria 0atment given immts: Mice were anon a Bruker 4.7

enoid coils with hted sagittal MRumber of slices=512 X 256, num

ormed using thC) editing sequem thick center s24 data points, formed in Matlaed using the p

d animals werbe-1, HPI) and H

y. These agent hour before sac

ere excised, emand stored at −8ome (Microm Intocked in SuperbAnalysis: The lathe lactate conte

The non-treated ttle effect on tumhe control and AAdria). At day 6

centrations than ese groups comT11 vs Adria). Hity, reduced vascdria-treated tumos, the tissue appe trend toward reis probably due tistology. er treatment, a r

CPT-11-treated Blactate concenspeculate that

sion to a less gf topoisomerase by complexing w’s induction of C(1). 1. Brill E, Gob-705. Epub 2011 F) pp. 203-11. 5. Mu

emotherapy n L. Zakian1 ancer Center, New

nstay of treatmek of effective cheed genes abnormadipocyte differed growth delay in

g evaluations. Fuut delay. Lactates to assess the ort was treated

were grown in thwas approximateume was monitod mice (V= (π/6day 1 (baseline),CPT-11 treated0.9 mg/kg i.p., Cmediately after thnesthetized with 7-T Biospec Spediameters of 10R images were10, FOV =24 mm

mber of acquisitiohe Selective Mence (4,5). Lactaslice with TR = 2

and spectral wab (Natick, MA)phantom substitre injected witHoechst 33342 (ts were dissolvcrifice (PIMO) an

mbedded in cuttin80°C. 10μm thicternational GmbHblock-PBS (Piercactate peak area

ent of a phantom umors grew mor

mor growth. On dAdria groups (P =6, the CPT-11 tre

the control anpared to baselinistologic and IHCularization (Hoecors at 1 week. Ipeared fairly hoeduced lactate cto reduced cell d

reduction in lactaBWH dedifferentitration is reducet CEBPα’s rol

glycolytic phenotI, resulting in do

with DNA and inCEBPα expressbble R, Angeles C,eb 18 3. Angeles Curuganandham M,

w York, NY, United

ent. However, themotherapy of demally expressed ientiation, is unden DDLS cells anurthermore, in the, an end-producchange in lactatwith doxorubici

he flanks of SCIDely 100 mm3. Fored in 7 control, 6)* L * W * D, day 3 and day mice. The micCPT11 100mg/khe baseline MRSIsoflurane durin

ectrometer. Tw mm and 14 mm

e collected (slicm, TR = 3000msons = 4). Lactat

Multiple Quantumate spectra wer2 sec, number oidth of 2510 Hz). Quantitation otution techniqueth PimonidazolSigma-Aldrich) a

ved in PBS annd 5 minutes pre

ng medium (OCTk frozen sectionH). Sections werce, USA) followea was normalizesection of know

re rapidly than thday 3, the CPT1= 0.001 for CPT1eated tumors sti

nd Adria groupsne ( P<0.0001 foC analysis (Fig. 2chst) and hypoxin contrast, in thmogeneous, we

concentration at density and/or th

ate was observeated liposarcomed by CPT-11 ile in promotintype. In additionouble-strand DNAterfering with thion may result i, et. al. Cancer ResCV, Laxa B, et. al.Koutcher JA, et. a

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3059Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)